Special Issue "Creatine Supplementation for Health and Clinical Diseases"

A special issue of Nutrients (ISSN 2072-6643). This special issue belongs to the section "Sports Nutrition".

Deadline for manuscript submissions: 31 December 2021.

Special Issue Editors

Prof. Dr. Richard B. Kreider
E-Mail Website
Guest Editor
Exercise & Sport Nutrition Laboratory, Human Clinical Research Facility, Texas A&M University, College Station, TX 77843, USA
Interests: exercise physiology; sports nutrition; performance enhancement; weight loss; women's health
Special Issues, Collections and Topics in MDPI journals
Dr. Jeffrey R. Stout
E-Mail Website
Guest Editor
Physiology of Work and Exercise Response (POWER) Laboratory, Institute of Exercise Physiology and Rehabilitation Science, School of Kinesiology and Physical Therapy University of Central Florida, 12494 University Blvd., Orlando, FL 32816, USA
Interests: nutrition; ergogenic aids; dietary supplements; body composition; muscle fatigue

Special Issue Information

Dear Colleagues,

Creatine supplementation is one of the most studied and effective ergogenic aids for athletes. The multifaceted mechanisms by which creatine exerts its beneficial effect include increasing anaerobic energy capacity, increasing protein synthesis, and decreasing protein breakdown, leading to increased muscle mass and physical performance. While these well-recognized creatine effects benefit the athlete, creatine may also serve as a potential clinical and therapeutic supplementary treatment to conventional medical interventions. Several studies have examined the effects on conditions such as diabetes, sarcopenia, osteoporosis, cancer, rehabilitation, and pulmonary and cardiovascular health. This Special Issue aims to provide comprehensive reviews of creatine supplementation effects for health and clinical diseases.

Dr. Richard B. Kreider
Dr. Jeffrey R. Stout
Guest Editors

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Keywords

  • creatine
  • neurodegeneration
  • muscular diseases
  • metabolic dysfunction
  • aging
  • cognition
  • rehabilitation

Published Papers (23 papers)

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Research

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Article
A Convergent Functional Genomics Analysis to Identify Biological Regulators Mediating Effects of Creatine Supplementation
Nutrients 2021, 13(8), 2521; https://0-doi-org.brum.beds.ac.uk/10.3390/nu13082521 - 23 Jul 2021
Viewed by 1464
Abstract
Creatine (Cr) and phosphocreatine (PCr) are physiologically essential molecules for life, given they serve as rapid and localized support of energy- and mechanical-dependent processes. This evolutionary advantage is based on the action of creatine kinase (CK) isozymes that connect places of ATP synthesis [...] Read more.
Creatine (Cr) and phosphocreatine (PCr) are physiologically essential molecules for life, given they serve as rapid and localized support of energy- and mechanical-dependent processes. This evolutionary advantage is based on the action of creatine kinase (CK) isozymes that connect places of ATP synthesis with sites of ATP consumption (the CK/PCr system). Supplementation with creatine monohydrate (CrM) can enhance this system, resulting in well-known ergogenic effects and potential health or therapeutic benefits. In spite of our vast knowledge about these molecules, no integrative analysis of molecular mechanisms under a systems biology approach has been performed to date; thus, we aimed to perform for the first time a convergent functional genomics analysis to identify biological regulators mediating the effects of Cr supplementation in health and disease. A total of 35 differentially expressed genes were analyzed. We identified top-ranked pathways and biological processes mediating the effects of Cr supplementation. The impact of CrM on miRNAs merits more research. We also cautiously suggest two dose–response functional pathways (kinase- and ubiquitin-driven) for the regulation of the Cr uptake. Our functional enrichment analysis, the knowledge-based pathway reconstruction, and the identification of hub nodes provide meaningful information for future studies. This work contributes to a better understanding of the well-reported benefits of Cr in sports and its potential in health and disease conditions, although further clinical research is needed to validate the proposed mechanisms. Full article
(This article belongs to the Special Issue Creatine Supplementation for Health and Clinical Diseases)
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Article
Creatine Monohydrate Supplementation Increases White Adipose Tissue Mitochondrial Markers in Male and Female Rats in a Depot Specific Manner
Nutrients 2021, 13(7), 2406; https://0-doi-org.brum.beds.ac.uk/10.3390/nu13072406 - 14 Jul 2021
Cited by 1 | Viewed by 1035
Abstract
White adipose tissue (WAT) is a dynamic endocrine organ that can play a significant role in thermoregulation. WAT has the capacity to adopt structural and functional characteristics of the more metabolically active brown adipose tissue (BAT) and contribute to non-shivering thermogenesis under specific [...] Read more.
White adipose tissue (WAT) is a dynamic endocrine organ that can play a significant role in thermoregulation. WAT has the capacity to adopt structural and functional characteristics of the more metabolically active brown adipose tissue (BAT) and contribute to non-shivering thermogenesis under specific stimuli. Non-shivering thermogenesis was previously thought to be uncoupling protein 1 (UCP1)-dependent however, recent evidence suggests that UCP1-independent mechanisms of thermogenesis exist. Namely, futile creatine cycling has been identified as a contributor to WAT thermogenesis. The purpose of this study was to examine the efficacy of creatine supplementation to alter mitochondrial markers as well as adipocyte size and multilocularity in inguinal (iWAT), gonadal (gWAT), and BAT. Thirty-two male and female Sprague-Dawley rats were treated with varying doses (0 g/L, 2.5 g/L, 5 g/L, and 10 g/L) of creatine monohydrate for 8 weeks. We demonstrate that mitochondrial markers respond in a sex and depot specific manner. In iWAT, female rats displayed significant increases in COXIV, PDH-E1alpha, and cytochrome C protein content. Male rats exhibited gWAT specific increases in COXIV and PDH-E1alpha protein content. This study supports creatine supplementation as a potential method of UCP1-independant thermogenesis and highlights the importance of taking a sex-specific approach when examining the efficacy of browning therapeutics in future research. Full article
(This article belongs to the Special Issue Creatine Supplementation for Health and Clinical Diseases)
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Article
Creatine Enhances the Effects of Cluster-Set Resistance Training on Lower-Limb Body Composition and Strength in Resistance-Trained Men: A Pilot Study
Nutrients 2021, 13(7), 2303; https://0-doi-org.brum.beds.ac.uk/10.3390/nu13072303 - 04 Jul 2021
Cited by 1 | Viewed by 1773
Abstract
Creatine monohydrate (CrM) supplementation has been shown to improve body composition and muscle strength when combined with resistance training (RT); however, no study has evaluated the combination of this nutritional strategy with cluster-set resistance training (CS-RT). The purpose of this pilot study was [...] Read more.
Creatine monohydrate (CrM) supplementation has been shown to improve body composition and muscle strength when combined with resistance training (RT); however, no study has evaluated the combination of this nutritional strategy with cluster-set resistance training (CS-RT). The purpose of this pilot study was to evaluate the effects of CrM supplementation during a high-protein diet and a CS-RT program on lower-limb fat-free mass (LL-FFM) and muscular strength. Twenty-three resistance-trained men (>2 years of training experience, 26.6 ± 8.1 years, 176.3 ± 6.8 cm, 75.6 ± 8.9 kg) participated in this study. Subjects were randomly allocated to a CS-RT+CrM (n = 8), a CS-RT (n = 8), or a control group (n = 7). The CS-RT+CrM group followed a CrM supplementation protocol with 0.1 g·kg−1·day−1 over eight weeks. Two sessions per week of lower-limb CS-RT were performed. LL-FFM corrected for fat-free adipose tissue (dual-energy X-ray absorptiometry) and muscle strength (back squat 1 repetition maximum (SQ-1RM) and countermovement jump (CMJ)) were measured pre- and post-intervention. Significant improvements were found in whole-body fat mass, fat percentage, LL-fat mass, LL-FFM, and SQ-1RM in the CS-RT+CrM and CS-RT groups; however, larger effect sizes were obtained in the CS-RT+CrM group regarding whole body FFM (0.64 versus 0.16), lower-limb FFM (0.62 versus 0.18), and SQ-1RM (1.23 versus 0.75) when compared to the CS-RT group. CMJ showed a significant improvement in the CS-RT+CrM group with no significant changes in CS-RT or control groups. No significant differences were found between groups. Eight weeks of CrM supplementation plus a high-protein diet during a CS-RT program has a higher clinical meaningfulness on lower-limb body composition and strength-related variables in trained males than CS-RT alone. Further research might study the potential health and therapeutic effects of this nutrition and exercise strategy. Full article
(This article belongs to the Special Issue Creatine Supplementation for Health and Clinical Diseases)
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Article
Relationship between Dietary Creatine and Growth Indicators in Children and Adolescents Aged 2–19 Years: A Cross-Sectional Study
Nutrients 2021, 13(3), 1027; https://0-doi-org.brum.beds.ac.uk/10.3390/nu13031027 - 23 Mar 2021
Cited by 3 | Viewed by 1692
Abstract
A possible role of dietary creatine for ensuring proper growth and development remains unknown. The main aim of this cross-sectional study was to quantify the amount of creatine consumed through regular diet among U.S. children and adolescents aged 2 to 19 years and [...] Read more.
A possible role of dietary creatine for ensuring proper growth and development remains unknown. The main aim of this cross-sectional study was to quantify the amount of creatine consumed through regular diet among U.S. children and adolescents aged 2 to 19 years and investigate the relationship between creatine intake and growth indicators, using data from the 2001–2002 National Health and Nutrition Examination Survey (NHANES). We included data for NHANES 2001–2002 respondents (4291 participants, 2133 boys and 2158 girls) aged 2 to 19 years at the time of screening, who provided valid dietary information and examination measures (standing height and weight). Individual values for total grams of creatine consumed per day for each participant were computed using the average amount of creatine (3.88 g/kg) across all sources of meat-based foods. All participants were categorized for height-for-age and BMI-for-age categories. The average daily intake of creatine across the whole sample was 1.07 ± 1.07 g (95% CI, from 1.04 to 1.10). Height, weight, and BMI were significantly different across creatine quartiles (p < 0.001), with all measures significantly higher in the 4th quartile of creatine intake (≥1.5 g/day) than those in other quartiles (p < 0.05). The participants from the 3rd quartile of creatine intake (0.84–1.49 g/day) were significantly different from others with respect to having lower rates of normal stature and higher rates of tall stature (p < 0.05). Each additional 0.1 g of creatine consumed per day increases height by 0.60 cm (simple model) or 0.30 cm (adjusted model). The daily intake of creatine from a regular diet in taller children and adolescents was higher than in shorter peers aged 2–19 years. Future research has to monitor temporal changes in growth and dietary creatine and validate our findings in interventional studies across pediatric populations. Full article
(This article belongs to the Special Issue Creatine Supplementation for Health and Clinical Diseases)
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Review

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Review
Timing of Creatine Supplementation around Exercise: A Real Concern?
Nutrients 2021, 13(8), 2844; https://0-doi-org.brum.beds.ac.uk/10.3390/nu13082844 - 19 Aug 2021
Viewed by 3119
Abstract
Creatine has been considered an effective ergogenic aid for several decades; it can help athletes engaged in a variety of sports and obtain performance gains. Creatine supplementation increases muscle creatine stores; several factors have been identified that may modify the intramuscular increase and [...] Read more.
Creatine has been considered an effective ergogenic aid for several decades; it can help athletes engaged in a variety of sports and obtain performance gains. Creatine supplementation increases muscle creatine stores; several factors have been identified that may modify the intramuscular increase and subsequent performance benefits, including baseline muscle Cr content, type II muscle fibre content and size, habitual dietary intake of Cr, aging, and exercise. Timing of creatine supplementation in relation to exercise has recently been proposed as an important consideration to optimise muscle loading and performance gains, although current consensus is lacking regarding the ideal ingestion time. Research has shifted towards comparing creatine supplementation strategies pre-, during-, or post-exercise. Emerging evidence suggests greater benefits when creatine is consumed after exercise compared to pre-exercise, although methodological limitations currently preclude solid conclusions. Furthermore, physiological and mechanistic data are lacking, in regard to claims that the timing of creatine supplementation around exercise moderates gains in muscle creatine and exercise performance. This review discusses novel scientific evidence on the timing of creatine intake, the possible mechanisms that may be involved, and whether the timing of creatine supplementation around exercise is truly a real concern. Full article
(This article belongs to the Special Issue Creatine Supplementation for Health and Clinical Diseases)
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Review
Chronic Dialysis Patients Are Depleted of Creatine: Review and Rationale for Intradialytic Creatine Supplementation
Nutrients 2021, 13(8), 2709; https://0-doi-org.brum.beds.ac.uk/10.3390/nu13082709 - 06 Aug 2021
Viewed by 951
Abstract
There is great need for the identification of new, potentially modifiable risk factors for the poor health-related quality of life (HRQoL) and of the excess risk of mortality in dialysis-dependent chronic kidney disease patients. Creatine is an essential contributor to cellular energy homeostasis, [...] Read more.
There is great need for the identification of new, potentially modifiable risk factors for the poor health-related quality of life (HRQoL) and of the excess risk of mortality in dialysis-dependent chronic kidney disease patients. Creatine is an essential contributor to cellular energy homeostasis, yet, on a daily basis, 1.6–1.7% of the total creatine pool is non-enzymatically degraded to creatinine and subsequently lost via urinary excretion, thereby necessitating a continuous supply of new creatine in order to remain in steady-state. Because of an insufficient ability to synthesize creatine, unopposed losses to the dialysis fluid, and insufficient intake due to dietary recommendations that are increasingly steered towards more plant-based diets, hemodialysis patients are prone to creatine deficiency, and may benefit from creatine supplementation. To avoid problems with compliance and fluid balance, and, furthermore, to prevent intradialytic losses of creatine to the dialysate, we aim to investigate the potential of intradialytic creatine supplementation in improving outcomes. Given the known physiological effects of creatine, intradialytic creatine supplementation may help to maintain creatine homeostasis among dialysis-dependent chronic kidney disease patients, and consequently improve muscle status, nutritional status, neurocognitive status, HRQoL. Additionally, we describe the rationale and design for a block-randomized, double-blind, placebo-controlled pilot study. The aim of the pilot study is to explore the creatine uptake in the circulation and tissues following different creatine supplementation dosages. Full article
(This article belongs to the Special Issue Creatine Supplementation for Health and Clinical Diseases)
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Review
Creatine for Exercise and Sports Performance, with Recovery Considerations for Healthy Populations
Nutrients 2021, 13(6), 1915; https://0-doi-org.brum.beds.ac.uk/10.3390/nu13061915 - 02 Jun 2021
Cited by 1 | Viewed by 3247
Abstract
Creatine is one of the most studied and popular ergogenic aids for athletes and recreational weightlifters seeking to improve sport and exercise performance, augment exercise training adaptations, and mitigate recovery time. Studies consistently reveal that creatine supplementation exerts positive ergogenic effects on single [...] Read more.
Creatine is one of the most studied and popular ergogenic aids for athletes and recreational weightlifters seeking to improve sport and exercise performance, augment exercise training adaptations, and mitigate recovery time. Studies consistently reveal that creatine supplementation exerts positive ergogenic effects on single and multiple bouts of short-duration, high-intensity exercise activities, in addition to potentiating exercise training adaptations. In this respect, supplementation consistently demonstrates the ability to enlarge the pool of intracellular creatine, leading to an amplification of the cell’s ability to resynthesize adenosine triphosphate. This intracellular expansion is associated with several performance outcomes, including increases in maximal strength (low-speed strength), maximal work output, power production (high-speed strength), sprint performance, and fat-free mass. Additionally, creatine supplementation may speed up recovery time between bouts of intense exercise by mitigating muscle damage and promoting the faster recovery of lost force-production potential. Conversely, contradictory findings exist in the literature regarding the potential ergogenic benefits of creatine during intermittent and continuous endurance-type exercise, as well as in those athletic tasks where an increase in body mass may hinder enhanced performance. The purpose of this review was to summarize the existing literature surrounding the efficacy of creatine supplementation on exercise and sports performance, along with recovery factors in healthy populations. Full article
(This article belongs to the Special Issue Creatine Supplementation for Health and Clinical Diseases)
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Review
Meta-Analysis Examining the Importance of Creatine Ingestion Strategies on Lean Tissue Mass and Strength in Older Adults
Nutrients 2021, 13(6), 1912; https://0-doi-org.brum.beds.ac.uk/10.3390/nu13061912 - 02 Jun 2021
Cited by 3 | Viewed by 2044
Abstract
Creatine supplementation in conjunction with resistance training (RT) augments gains in lean tissue mass and strength in aging adults; however, there is a large amount of heterogeneity between individual studies that may be related to creatine ingestion strategies. Therefore, the purpose of this [...] Read more.
Creatine supplementation in conjunction with resistance training (RT) augments gains in lean tissue mass and strength in aging adults; however, there is a large amount of heterogeneity between individual studies that may be related to creatine ingestion strategies. Therefore, the purpose of this review was to (1) perform updated meta-analyses comparing creatine vs. placebo (independent of dosage and frequency of ingestion) during a resistance training program on measures of lean tissue mass and strength, (2) perform meta-analyses examining the effects of different creatine dosing strategies (lower: ≤5 g/day and higher: >5 g/day), with and without a creatine-loading phase (≥20 g/day for 5–7 days), and (3) perform meta-analyses determining whether creatine supplementation only on resistance training days influences measures of lean tissue mass and strength. Overall, creatine (independent of dosing strategy) augments lean tissue mass and strength increase from RT vs. placebo. Subanalyses showed that creatine-loading followed by lower-dose creatine (≤5 g/day) increased chest press strength vs. placebo. Higher-dose creatine (>5 g/day), with and without a creatine-loading phase, produced significant gains in leg press strength vs. placebo. However, when studies involving a creatine-loading phase were excluded from the analyses, creatine had no greater effect on chest press or leg press strength vs. placebo. Finally, creatine supplementation only on resistance training days significantly increased measures of lean tissue mass and strength vs. placebo. Full article
(This article belongs to the Special Issue Creatine Supplementation for Health and Clinical Diseases)
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Review
The Application of Creatine Supplementation in Medical Rehabilitation
Nutrients 2021, 13(6), 1825; https://0-doi-org.brum.beds.ac.uk/10.3390/nu13061825 - 27 May 2021
Cited by 2 | Viewed by 3583
Abstract
Numerous health conditions affecting the musculoskeletal, cardiopulmonary, and nervous systems can result in physical dysfunction, impaired performance, muscle weakness, and disuse-induced atrophy. Due to its well-documented anabolic potential, creatine monohydrate has been investigated as a supplemental agent to mitigate the loss of muscle [...] Read more.
Numerous health conditions affecting the musculoskeletal, cardiopulmonary, and nervous systems can result in physical dysfunction, impaired performance, muscle weakness, and disuse-induced atrophy. Due to its well-documented anabolic potential, creatine monohydrate has been investigated as a supplemental agent to mitigate the loss of muscle mass and function in a variety of acute and chronic conditions. A review of the literature was conducted to assess the current state of knowledge regarding the effects of creatine supplementation on rehabilitation from immobilization and injury, neurodegenerative diseases, cardiopulmonary disease, and other muscular disorders. Several of the findings are encouraging, showcasing creatine’s potential efficacy as a supplemental agent via preservation of muscle mass, strength, and physical function; however, the results are not consistent. For multiple diseases, only a few creatine studies with small sample sizes have been published, making it difficult to draw definitive conclusions. Rationale for discordant findings is further complicated by differences in disease pathologies, intervention protocols, creatine dosing and duration, and patient population. While creatine supplementation demonstrates promise as a therapeutic aid, more research is needed to fill gaps in knowledge within medical rehabilitation. Full article
(This article belongs to the Special Issue Creatine Supplementation for Health and Clinical Diseases)
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Review
Creatine in T Cell Antitumor Immunity and Cancer Immunotherapy
by and
Nutrients 2021, 13(5), 1633; https://0-doi-org.brum.beds.ac.uk/10.3390/nu13051633 - 13 May 2021
Cited by 4 | Viewed by 1477
Abstract
Creatine is a broadly used dietary supplement that has been extensively studied for its benefit on the musculoskeletal system. Yet, there is limited knowledge regarding the metabolic regulation of creatine in cells beyond the muscle. New insights concerning various regulatory functions for creatine [...] Read more.
Creatine is a broadly used dietary supplement that has been extensively studied for its benefit on the musculoskeletal system. Yet, there is limited knowledge regarding the metabolic regulation of creatine in cells beyond the muscle. New insights concerning various regulatory functions for creatine in other physiological systems are developing. Here, we highlight the latest advances in understanding creatine regulation of T cell antitumor immunity, a topic that has previously gained little attention in the creatine research field. Creatine has been identified as an important metabolic regulator conserving bioenergy to power CD8 T cell antitumor reactivity in a tumor microenvironment; creatine supplementation has been shown to enhance antitumor T cell immunity in multiple preclinical mouse tumor models and, importantly, to synergize with other cancer immunotherapy modalities, such as the PD-1/PD-L1 blockade therapy, to improve antitumor efficacy. The potential application of creatine supplementation for cancer immunotherapy and the relevant considerations are discussed. Full article
(This article belongs to the Special Issue Creatine Supplementation for Health and Clinical Diseases)
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Review
Creatine Supplementation for Patients with Inflammatory Bowel Diseases: A Scientific Rationale for a Clinical Trial
Nutrients 2021, 13(5), 1429; https://0-doi-org.brum.beds.ac.uk/10.3390/nu13051429 - 23 Apr 2021
Cited by 2 | Viewed by 1880
Abstract
Based on theoretical considerations, experimental data with cells in vitro, animal studies in vivo, as well as a single case pilot study with one colitis patient, a consolidated hypothesis can be put forward, stating that “oral supplementation with creatine monohydrate (Cr), a pleiotropic [...] Read more.
Based on theoretical considerations, experimental data with cells in vitro, animal studies in vivo, as well as a single case pilot study with one colitis patient, a consolidated hypothesis can be put forward, stating that “oral supplementation with creatine monohydrate (Cr), a pleiotropic cellular energy precursor, is likely to be effective in inducing a favorable response and/or remission in patients with inflammatory bowel diseases (IBD), like ulcerative colitis and/or Crohn’s disease”. A current pilot clinical trial that incorporates the use of oral Cr at a dose of 2 × 7 g per day, over an initial period of 2 months in conjunction with ongoing therapies (NCT02463305) will be informative for the proposed larger, more long-term Cr supplementation study of 2 × 3–5 g of Cr per day for a time of 3–6 months. This strategy should be insightful to the potential for Cr in reducing or alleviating the symptoms of IBD. Supplementation with chemically pure Cr, a natural nutritional supplement, is well tolerated not only by healthy subjects, but also by patients with diverse neuromuscular diseases. If the outcome of such a clinical pilot study with Cr as monotherapy or in conjunction with metformin were positive, oral Cr supplementation could then be used in the future as potentially useful adjuvant therapeutic intervention for patients with IBD, preferably together with standard medication used for treating patients with chronic ulcerative colitis and/or Crohn’s disease. Full article
(This article belongs to the Special Issue Creatine Supplementation for Health and Clinical Diseases)
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Review
Metabolic Basis of Creatine in Health and Disease: A Bioinformatics-Assisted Review
Nutrients 2021, 13(4), 1238; https://0-doi-org.brum.beds.ac.uk/10.3390/nu13041238 - 09 Apr 2021
Cited by 7 | Viewed by 3150
Abstract
Creatine (Cr) is a ubiquitous molecule that is synthesized mainly in the liver, kidneys, and pancreas. Most of the Cr pool is found in tissues with high-energy demands. Cr enters target cells through a specific symporter called Na+/Cl-dependent Cr [...] Read more.
Creatine (Cr) is a ubiquitous molecule that is synthesized mainly in the liver, kidneys, and pancreas. Most of the Cr pool is found in tissues with high-energy demands. Cr enters target cells through a specific symporter called Na+/Cl-dependent Cr transporter (CRT). Once within cells, creatine kinase (CK) catalyzes the reversible transphosphorylation reaction between [Mg2+:ATP4−]2− and Cr to produce phosphocreatine (PCr) and [Mg2+:ADP3−]. We aimed to perform a comprehensive and bioinformatics-assisted review of the most recent research findings regarding Cr metabolism. Specifically, several public databases, repositories, and bioinformatics tools were utilized for this endeavor. Topics of biological complexity ranging from structural biology to cellular dynamics were addressed herein. In this sense, we sought to address certain pre-specified questions including: (i) What happens when creatine is transported into cells? (ii) How is the CK/PCr system involved in cellular bioenergetics? (iii) How is the CK/PCr system compartmentalized throughout the cell? (iv) What is the role of creatine amongst different tissues? and (v) What is the basis of creatine transport? Under the cellular allostasis paradigm, the CK/PCr system is physiologically essential for life (cell survival, growth, proliferation, differentiation, and migration/motility) by providing an evolutionary advantage for rapid, local, and temporal support of energy- and mechanical-dependent processes. Thus, we suggest the CK/PCr system acts as a dynamic biosensor based on chemo-mechanical energy transduction, which might explain why dysregulation in Cr metabolism contributes to a wide range of diseases besides the mitigating effect that Cr supplementation may have in some of these disease states. Full article
(This article belongs to the Special Issue Creatine Supplementation for Health and Clinical Diseases)
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Review
Role of Creatine in the Heart: Health and Disease
Nutrients 2021, 13(4), 1215; https://0-doi-org.brum.beds.ac.uk/10.3390/nu13041215 - 07 Apr 2021
Cited by 5 | Viewed by 1989
Abstract
Creatine is a key player in heart contraction and energy metabolism. Creatine supplementation (throughout the paper, only supplementation with creatine monohydrate will be reviewed, as this is by far the most used and best-known way of supplementing creatine) increases creatine content even in [...] Read more.
Creatine is a key player in heart contraction and energy metabolism. Creatine supplementation (throughout the paper, only supplementation with creatine monohydrate will be reviewed, as this is by far the most used and best-known way of supplementing creatine) increases creatine content even in the normal heart, and it is generally safe. In heart failure, creatine and phosphocreatine decrease because of decreased expression of the creatine transporter, and because phosphocreatine degrades to prevent adenosine triphosphate (ATP) exhaustion. This causes decreased contractility reserve of the myocardium and correlates with left ventricular ejection fraction, and it is a predictor of mortality. Thus, there is a strong rationale to supplement with creatine the failing heart. Pending additional trials, creatine supplementation in heart failure may be useful given data showing its effectiveness (1) against specific parameters of heart failure, and (2) against the decrease in muscle strength and endurance of heart failure patients. In heart ischemia, the majority of trials used phosphocreatine, whose mechanism of action is mostly unrelated to changes in the ergogenic creatine-phosphocreatine system. Nevertheless, preliminary data with creatine supplementation are encouraging, and warrant additional studies. Prevention of cardiac toxicity of the chemotherapy compounds anthracyclines is a novel field where creatine supplementation may also be useful. Creatine effectiveness in this case may be because anthracyclines reduce expression of the creatine transporter, and because of the pleiotropic antioxidant properties of creatine. Moreover, creatine may also reduce concomitant muscle damage by anthracyclines. Full article
(This article belongs to the Special Issue Creatine Supplementation for Health and Clinical Diseases)
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Review
Creatine Supplementation in Women’s Health: A Lifespan Perspective
Nutrients 2021, 13(3), 877; https://0-doi-org.brum.beds.ac.uk/10.3390/nu13030877 - 08 Mar 2021
Cited by 2 | Viewed by 5494
Abstract
Despite extensive research on creatine, evidence for use among females is understudied. Creatine characteristics vary between males and females, with females exhibiting 70–80% lower endogenous creatine stores compared to males. Understanding creatine metabolism pre- and post-menopause yields important implications for creatine supplementation for [...] Read more.
Despite extensive research on creatine, evidence for use among females is understudied. Creatine characteristics vary between males and females, with females exhibiting 70–80% lower endogenous creatine stores compared to males. Understanding creatine metabolism pre- and post-menopause yields important implications for creatine supplementation for performance and health among females. Due to the hormone-related changes to creatine kinetics and phosphocreatine resynthesis, supplementation may be particularly important during menses, pregnancy, post-partum, during and post-menopause. Creatine supplementation among pre-menopausal females appears to be effective for improving strength and exercise performance. Post-menopausal females may also experience benefits in skeletal muscle size and function when consuming high doses of creatine (0.3 g·kg−1·d−1); and favorable effects on bone when combined with resistance training. Pre-clinical and clinical evidence indicates positive effects from creatine supplementation on mood and cognition, possibly by restoring brain energy levels and homeostasis. Creatine supplementation may be even more effective for females by supporting a pro-energetic environment in the brain. The purpose of this review was to highlight the use of creatine in females across the lifespan with particular emphasis on performance, body composition, mood, and dosing strategies. Full article
(This article belongs to the Special Issue Creatine Supplementation for Health and Clinical Diseases)
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Review
The Potential Role of Creatine in Vascular Health
Nutrients 2021, 13(3), 857; https://0-doi-org.brum.beds.ac.uk/10.3390/nu13030857 - 05 Mar 2021
Cited by 4 | Viewed by 2672
Abstract
Creatine is an organic compound, consumed exogenously in the diet and synthesized endogenously via an intricate inter-organ process. Functioning in conjunction with creatine kinase, creatine has long been known for its pivotal role in cellular energy provision and energy shuttling. In addition to [...] Read more.
Creatine is an organic compound, consumed exogenously in the diet and synthesized endogenously via an intricate inter-organ process. Functioning in conjunction with creatine kinase, creatine has long been known for its pivotal role in cellular energy provision and energy shuttling. In addition to the abundance of evidence supporting the ergogenic benefits of creatine supplementation, recent evidence suggests a far broader application for creatine within various myopathies, neurodegenerative diseases, and other pathologies. Furthermore, creatine has been found to exhibit non-energy related properties, contributing as a possible direct and in-direct antioxidant and eliciting anti-inflammatory effects. In spite of the new clinical success of supplemental creatine, there is little scientific insight into the potential effects of creatine on cardiovascular disease (CVD), the leading cause of mortality. Taking into consideration the non-energy related actions of creatine, highlighted in this review, it can be speculated that creatine supplementation may serve as an adjuvant therapy for the management of vascular health in at-risk populations. This review, therefore, not only aims to summarize the current literature surrounding creatine and vascular health, but to also shed light onto the potential mechanisms in which creatine may be able to serve as a beneficial supplement capable of imparting vascular-protective properties and promoting vascular health. Full article
(This article belongs to the Special Issue Creatine Supplementation for Health and Clinical Diseases)
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Review
The Role of Creatine in the Development and Activation of Immune Responses
Nutrients 2021, 13(3), 751; https://0-doi-org.brum.beds.ac.uk/10.3390/nu13030751 - 26 Feb 2021
Cited by 6 | Viewed by 1996
Abstract
The use of dietary supplements has become increasingly common over the past 20 years. Whereas supplements were formerly used mainly by elite athletes, age and fitness status no longer dictates who uses these substances. Indeed, many nutritional supplements are recommended by health care [...] Read more.
The use of dietary supplements has become increasingly common over the past 20 years. Whereas supplements were formerly used mainly by elite athletes, age and fitness status no longer dictates who uses these substances. Indeed, many nutritional supplements are recommended by health care professionals to their patients. Creatine (CR) is a widely used dietary supplement that has been well-studied for its effects on performance and health. CR also aids in recovery from strenuous bouts of exercise by reducing inflammation. Although CR is considered to be very safe in recommended doses, a caveat is that a preponderance of the studies have focused upon young athletic individuals; thus there is limited knowledge regarding the effects of CR on children or the elderly. In this review, we examine the potential of CR to impact the host outside of the musculoskeletal system, specifically, the immune system, and discuss the available data demonstrating that CR can impact both innate and adaptive immune responses, together with how the effects on the immune system might be exploited to enhance human health. Full article
(This article belongs to the Special Issue Creatine Supplementation for Health and Clinical Diseases)
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Review
Current Evidence and Possible Future Applications of Creatine Supplementation for Older Adults
Nutrients 2021, 13(3), 745; https://0-doi-org.brum.beds.ac.uk/10.3390/nu13030745 - 26 Feb 2021
Cited by 6 | Viewed by 3346
Abstract
Sarcopenia, defined as age-related reduction in muscle mass, strength, and physical performance, is associated with other age-related health conditions such as osteoporosis, osteosarcopenia, sarcopenic obesity, physical frailty, and cachexia. From a healthy aging perspective, lifestyle interventions that may help overcome characteristics and associated [...] Read more.
Sarcopenia, defined as age-related reduction in muscle mass, strength, and physical performance, is associated with other age-related health conditions such as osteoporosis, osteosarcopenia, sarcopenic obesity, physical frailty, and cachexia. From a healthy aging perspective, lifestyle interventions that may help overcome characteristics and associated comorbidities of sarcopenia are clinically important. One possible intervention is creatine supplementation (CR). Accumulating research over the past few decades shows that CR, primarily when combined with resistance training (RT), has favourable effects on aging muscle, bone and fat mass, muscle and bone strength, and tasks of physical performance in healthy older adults. However, research is very limited regarding the efficacy of CR in older adults with sarcopenia or osteoporosis and no research exists in older adults with osteosarcopenia, sarcopenic obesity, physical frailty, or cachexia. Therefore, the purpose of this narrative review is (1) to evaluate and summarize current research involving CR, with and without RT, on properties of muscle and bone in older adults and (2) to provide a rationale and justification for future research involving CR in older adults with osteosarcopenia, sarcopenic obesity, physical frailty, or cachexia. Full article
(This article belongs to the Special Issue Creatine Supplementation for Health and Clinical Diseases)
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Review
Creatine Supplementation in Children and Adolescents
Nutrients 2021, 13(2), 664; https://0-doi-org.brum.beds.ac.uk/10.3390/nu13020664 - 18 Feb 2021
Cited by 4 | Viewed by 3341
Abstract
Creatine is a popular ergogenic aid among athletic populations with consistent evidence indicating that creatine supplementation also continues to be commonly used among adolescent populations. In addition, the evidence base supporting the therapeutic benefits of creatine supplementation for a plethora of clinical applications [...] Read more.
Creatine is a popular ergogenic aid among athletic populations with consistent evidence indicating that creatine supplementation also continues to be commonly used among adolescent populations. In addition, the evidence base supporting the therapeutic benefits of creatine supplementation for a plethora of clinical applications in both adults and children continues to grow. Among pediatric populations, a strong rationale exists for creatine to afford therapeutic benefits pertaining to multiple neuromuscular and metabolic disorders, with preliminary evidence for other subsets of clinical populations as well. Despite the strong evidence supporting the efficacy and safety of creatine supplementation among adult populations, less is known as to whether similar physiological benefits extend to children and adolescent populations, and in particular those adolescent populations who are regularly participating in high-intensity exercise training. While limited in scope, studies involving creatine supplementation and exercise performance in adolescent athletes generally report improvements in several ergogenic outcomes with limited evidence of ergolytic properties and consistent reports indicating no adverse events associated with supplementation. The purpose of this article is to summarize the rationale, prevalence of use, performance benefits, clinical applications, and safety of creatine use in children and adolescents. Full article
(This article belongs to the Special Issue Creatine Supplementation for Health and Clinical Diseases)
Review
Creatine Supplementation and Brain Health
Nutrients 2021, 13(2), 586; https://0-doi-org.brum.beds.ac.uk/10.3390/nu13020586 - 10 Feb 2021
Cited by 7 | Viewed by 6475
Abstract
There is a robust and compelling body of evidence supporting the ergogenic and therapeutic role of creatine supplementation in muscle. Beyond these well-described effects and mechanisms, there is literature to suggest that creatine may also be beneficial to brain health (e.g., cognitive processing, [...] Read more.
There is a robust and compelling body of evidence supporting the ergogenic and therapeutic role of creatine supplementation in muscle. Beyond these well-described effects and mechanisms, there is literature to suggest that creatine may also be beneficial to brain health (e.g., cognitive processing, brain function, and recovery from trauma). This is a growing field of research, and the purpose of this short review is to provide an update on the effects of creatine supplementation on brain health in humans. There is a potential for creatine supplementation to improve cognitive processing, especially in conditions characterized by brain creatine deficits, which could be induced by acute stressors (e.g., exercise, sleep deprivation) or chronic, pathologic conditions (e.g., creatine synthesis enzyme deficiencies, mild traumatic brain injury, aging, Alzheimer’s disease, depression). Despite this, the optimal creatine protocol able to increase brain creatine levels is still to be determined. Similarly, supplementation studies concomitantly assessing brain creatine and cognitive function are needed. Collectively, data available are promising and future research in the area is warranted. Full article
(This article belongs to the Special Issue Creatine Supplementation for Health and Clinical Diseases)
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Review
Potential of Creatine in Glucose Management and Diabetes
Nutrients 2021, 13(2), 570; https://0-doi-org.brum.beds.ac.uk/10.3390/nu13020570 - 09 Feb 2021
Cited by 5 | Viewed by 2406
Abstract
Creatine is one of the most popular supplements worldwide, and it is frequently used by both athletic and non-athletic populations to improve power, strength, muscle mass and performance. A growing body of evidence has been identified potential therapeutic effects of creatine in a [...] Read more.
Creatine is one of the most popular supplements worldwide, and it is frequently used by both athletic and non-athletic populations to improve power, strength, muscle mass and performance. A growing body of evidence has been identified potential therapeutic effects of creatine in a wide variety of clinical conditions, such as cancer, muscle dystrophy and neurodegenerative disorders. Evidence has suggested that creatine supplementation alone, and mainly in combination with exercise training, may improve glucose metabolism in health individuals and insulin-resistant individuals, such as in those with type 2 diabetes mellitus. Creatine itself may stimulate insulin secretion in vitro, improve muscle glycogen stores and ameliorate hyperglycemia in animals. In addition, exercise induces numerous metabolic benefits, including increases in insulin-independent muscle glucose uptake and insulin sensitivity. It has been speculated that creatine supplementation combined with exercise training could result in additional improvements in glucose metabolism when compared with each intervention separately. The possible mechanism underlying the effects of combined exercise and creatine supplementation is an enhanced glucose transport into muscle cell by type 4 glucose transporter (GLUT-4) translocation to sarcolemma. Although preliminary findings from small-scale trials involving patients with type 2 diabetes mellitus are promising, the efficacy of creatine for improving glycemic control is yet to be confirmed. In this review, we aim to explore the possible therapeutic role of creatine supplementation on glucose management and as a potential anti-diabetic intervention, summarizing the current knowledge and highlighting the research gaps. Full article
(This article belongs to the Special Issue Creatine Supplementation for Health and Clinical Diseases)
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Review
Diagnostic and Pharmacological Potency of Creatine in Post-Viral Fatigue Syndrome
Nutrients 2021, 13(2), 503; https://0-doi-org.brum.beds.ac.uk/10.3390/nu13020503 - 04 Feb 2021
Cited by 1 | Viewed by 4397
Abstract
Post-viral fatigue syndrome (PVFS) is a widespread chronic neurological disease with no definite etiological factor(s), no actual diagnostic test, and no approved pharmacological treatment, therapy, or cure. Among other features, PVFS could be accompanied by various irregularities in creatine metabolism, perturbing either tissue [...] Read more.
Post-viral fatigue syndrome (PVFS) is a widespread chronic neurological disease with no definite etiological factor(s), no actual diagnostic test, and no approved pharmacological treatment, therapy, or cure. Among other features, PVFS could be accompanied by various irregularities in creatine metabolism, perturbing either tissue levels of creatine in the brain, the rates of phosphocreatine resynthesis in the skeletal muscle, or the concentrations of the enzyme creatine kinase in the blood. Furthermore, supplemental creatine and related guanidino compounds appear to impact both patient- and clinician-reported outcomes in syndromes and maladies with chronic fatigue. This paper critically overviews the most common disturbances in creatine metabolism in various PVFS populations, summarizes human trials on dietary creatine and creatine analogs in the syndrome, and discusses new frontiers and open questions for using creatine in a post-COVID-19 world. Full article
(This article belongs to the Special Issue Creatine Supplementation for Health and Clinical Diseases)
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Review
Creatine Metabolism in Female Reproduction, Pregnancy and Newborn Health
Nutrients 2021, 13(2), 490; https://0-doi-org.brum.beds.ac.uk/10.3390/nu13020490 - 02 Feb 2021
Cited by 7 | Viewed by 2697
Abstract
Creatine metabolism is an important component of cellular energy homeostasis. Via the creatine kinase circuit, creatine derived from our diet or synthesized endogenously provides spatial and temporal maintenance of intracellular adenosine triphosphate (ATP) production; this is particularly important for cells with high or [...] Read more.
Creatine metabolism is an important component of cellular energy homeostasis. Via the creatine kinase circuit, creatine derived from our diet or synthesized endogenously provides spatial and temporal maintenance of intracellular adenosine triphosphate (ATP) production; this is particularly important for cells with high or fluctuating energy demands. The use of this circuit by tissues within the female reproductive system, as well as the placenta and the developing fetus during pregnancy is apparent throughout the literature, with some studies linking perturbations in creatine metabolism to reduced fertility and poor pregnancy outcomes. Maternal dietary creatine supplementation during pregnancy as a safeguard against hypoxia-induced perinatal injury, particularly that of the brain, has also been widely studied in pre-clinical in vitro and small animal models. However, there is still no consensus on whether creatine is essential for successful reproduction. This review consolidates the available literature on creatine metabolism in female reproduction, pregnancy and the early neonatal period. Creatine metabolism is discussed in relation to cellular bioenergetics and de novo synthesis, as well as the potential to use dietary creatine in a reproductive setting. We highlight the apparent knowledge gaps and the research “road forward” to understand, and then utilize, creatine to improve reproductive health and perinatal outcomes. Full article
(This article belongs to the Special Issue Creatine Supplementation for Health and Clinical Diseases)
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Review
Creatine in Health and Disease
Nutrients 2021, 13(2), 447; https://0-doi-org.brum.beds.ac.uk/10.3390/nu13020447 - 29 Jan 2021
Cited by 14 | Viewed by 6425
Abstract
Although creatine has been mostly studied as an ergogenic aid for exercise, training, and sport, several health and potential therapeutic benefits have been reported. This is because creatine plays a critical role in cellular metabolism, particularly during metabolically stressed states, and limitations in [...] Read more.
Although creatine has been mostly studied as an ergogenic aid for exercise, training, and sport, several health and potential therapeutic benefits have been reported. This is because creatine plays a critical role in cellular metabolism, particularly during metabolically stressed states, and limitations in the ability to transport and/or store creatine can impair metabolism. Moreover, increasing availability of creatine in tissue may enhance cellular metabolism and thereby lessen the severity of injury and/or disease conditions, particularly when oxygen availability is compromised. This systematic review assesses the peer-reviewed scientific and medical evidence related to creatine’s role in promoting general health as we age and how creatine supplementation has been used as a nutritional strategy to help individuals recover from injury and/or manage chronic disease. Additionally, it provides reasonable conclusions about the role of creatine on health and disease based on current scientific evidence. Based on this analysis, it can be concluded that creatine supplementation has several health and therapeutic benefits throughout the lifespan. Full article
(This article belongs to the Special Issue Creatine Supplementation for Health and Clinical Diseases)
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